The serological, in vitro cellular and genetic definition of DLA and non-DLA histocompatibility products within the selectively bred lines of dogs of known pedigree maintained within the restricted genetic pool of the Cooperstown colony will be continued. Progress made in the definition of these histocompatibility products will be applied directly to the selection of donor-recipient combinations for the induction of specific allogeneic unresponsiveness in adult dogs. The observation that supralethal total body irradiation and host reconstitution with stored autologous marrow can, if followed by early challenge of the host with a DLA-identical kidney allograft, produce long-term unresponsiveness to this organ will be extended, and an attempt will be made to develop similar states of allogeneic unresponsiveness in adult donor-recipient canine combinations under varying degrees of DLA compatibility. In this regard, an attempt will also be made to identify further the sharing of organ specific alloantigens between the kidney, pancreas, and other major transplantable organs. The information gained in the course of this year's studies with regard to the biological effects of supralethal total body irradiation will be extended to parallel studies of the potential effect of extracorporeal irradiation of blood upon immunobiological memory. These studies will be performed with special reference to the possibility that long-term radiation therapy may deprive the hyperimmunized host of his/her state of altered reactivity to tissue allografts. Such an observation may be of direct relevance to the return of patients currently on hemodialysis and exhibiting high titers of cytotoxic HLA antibodies to a normal state which would permit them to be once again eligible for renal allotransplantation. These studies will be performed in parallel with a continuing assessment of a wide variety of immuuosuppressive agents capable of potentiating the tolerogenic effects of supralethal total body irradiation and host reconstitution with autologous marrow.